The United States government has rights in this invention by virtue of grants from the National Science Foundation.
This is generally in the area of polymeric controlled drug delivery devices, and specifically in the area of polymer/Pluronic.TM. blends for controlled delivery.
Recently, a variety of biodegradable polymers have been widely used as implantable biomaterials, such as prosthetics and tissue support matrices, and as drug delivery devices. The main advantage of using the biodegradable polymer is that no retrieval of the device is needed after a particular usage. The degradation time of the polymer as well as the release properties of a particular drug from the polymer can also be varied, for example, from months to years and from linear to staggered release, by varying molecular weight and chemical composition of the polymer. The chemical composition is varied by selection of the monomers and copolymerization with other biodegradable monomers. The ratios of amorphous to crystalline and hydrophilic to hydrophobic properties are largely responsible for determining the degradation time.
Although widely used and approved for use in vivo by the United States Food and Drug Administration, it is difficult to obtain the desired release profile using many of these biocompatible, biodegradable polymers such as poly(lactic acid) (PLA). PLA is widely used since the degradation product, lactic acid, is metabolized in the body. There have been several studies on protein delivery using PLA as a matrix, in which a significant portion of the loaded protein was often released at the initial stage as a single burst, rather than over an extended period of time, regardless of the rate of degradation of the matrix.
Two methods have been utilized to improve the release profile of compounds from these polymers: copolymerization of the lactic acid with glycolic acid to form poly(lactide-glycolide) copolymers and mixing the compound encapsulated in PLA with the same compound encapsulated in other polymers or copolymers. However, neither method has been totally successful in achieving the desired release rate, or has proven to be difficult to control during manufacture and administration.
Due to processing considerations, the mechanical properties of the polymer are important. The polymer must be sufficiently hard but flexible to allow incorporation of drug, must be soluble in solvents not denaturing the protein to be encapsulated, or melt at a low enough temperature to allow incorporation of the drug without denaturation of the drug. These are particularly a problem with many of the heat labile drugs.
Polymer blends, a physical mixture of two different polymers, exhibit advantageous physical and mechanical properties that each individual polymer does not have. Depending on thermodynamic compatibilities of the two chosen polymers, different degrees of phase separated blends can be obtained. However, only a few applications of polymer blending technology for drug delivery matrices have been attempted, as reported by Younes and Cohn, European Polymer J. 11, 765 (1988). For example, PLA has been blended with degradable and nondegradable polymers such as poly(D-lactic acid), as reported by Loomis, et al., ACS Polymer Preprint 32, 55 (1990), poly(glycolic acid), as reported by Cha and Pitt, Biomaterials 11, 108-111 (1990), and poly(ethylene-vinyl acetate), as reported by Dollinger and Swan, ACS Polymer Preprint 32, 429 (1990), in an effort to modify PLA morphology and its degradation profile.
It is therefore an object of the present invention to provide biodegradable polymeric compositions for controlled drug delivery, and methods for making and using the compositions, wherein the compositions have desired mechanical and release properties as compared with PLA polymeric compositions for controlled drug delivery.